Cyanidin-3-O-glucoside attenuates high glucose-induced podocytes dysfunction by inhibiting apoptosis and promoting autophagy via activation of SIRT1/AMPK pathway

2020 ◽  
Author(s):  
Shu Wang ◽  
Yuqing Huang ◽  
Guangyan Luo ◽  
Xin Yang ◽  
Wei Huang
Keyword(s):  
High Glucose ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Epithelial Mesenchymal Transition ◽  
Flow Cytometry Assay ◽  
Mesenchymal Transition ◽  
Ampk Pathway ◽  
High Glucose Condition ◽  
The World ◽  
Glucose Condition

Diabetic nephropathy (DN) is a common and complicated chronic kidney disease around the world. To elucidate and find effective therapies of DN is of vital importance. In this paper, we have discovered that Cyanidin-3-O-glucoside (C3G), which is one of the anthocyanins, could alleviate high glucose induced podocytes dysfunction. MTT, flow cytometry assay and western blot analysis showed that C3G could reverse the increase of cell apoptosis under high glucose treatment in MPC5 cells by up-regulation of Bcl2 and down-regulation of Bax and cleaved-caspase 3. Moreover, C3G improved the autophagy decrease that was induced by high glucose through regulating the expression level of LC3 II/LC3 I, Beclin1 and p62. In addition, C3G inhibited epithelial-mesenchymal transition (EMT) by increasing E-cadherin and reducing Vimentin. By further mechanisms study, we found C3G activated the SIRT1 and AMPK which were inhibited in high glucose condition. Silencing SIRT1 blocked the effect of C3G on regulating cell apoptosis, autophagy and EMT. In summary, our current findings suggest the protective effect of C3G against high glucose induced podocytes dysfunction is by improving autophagy and reducing apoptosis and EMT via activating SIRT1/AMPK pathway. It might be a new insight for the treatment of DN.

scholarly journals LncRNA NEAT1 regulated diabetic retinal epithelial-mesenchymal transition through regulating miR-204/SOX4 axis

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11817
Author(s):  
Yang Yang ◽  
Jing Zhou ◽  
Wei hong Li ◽  
Zhi xiong Zhou ◽  
Xiao bo Xia
Keyword(s):  
High Glucose ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
High Glucose Condition ◽  
Gene Assay ◽  
Related Proteins ◽  
Lncrna Neat1 ◽  
Glucose Condition

Aim Epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells is the key of the development of diabetic retinopathy (DR), and lncRNA NEAT1 could accelerate EMT in diabetic nephropathy. Meanwhile, as a diabetes susceptibility gene, whether sex-determining region Y-related (SRY) high-mobility group box 4 (SOX4) has relationship with lncRNA NEAT1 in DR remains unclear. Methods Firstly, NEAT1, SOX4 and miR-204 were evaluated by qRT-PCR (quantitative reverse-transcriptase PCR) under high glucose condition. Then, cell viability, proliferation, migration and invasion were respectively detected by MTT, BrdU staining, wound healing and transwell assay after NEAT1 knockdown or miR-204 overexpression. Also, the EMT-related proteins were examined by western blot and cell immunofluorescence assay. In order to confirm the relationship between miR-204 and NEAT1 or SOX4, dual luciferase reporter gene assay was conducted. At the same time, the protein levels of SOX4 and EMT-related proteins were investigated by immunohistochemistry in vivo. Results High glucose upregulated NEAT1 and SOX4 and downregulated miR-204 in ARPE19 cells. NEAT1 knockdown or miR-204 overexpression inhibited the proliferation and EMT progression of ARPE19 cells induced by high glucose. NEAT1 was identified as a molecular sponge of miR-204 to increase the level of SOX4. The effect of NEAT1 knockdown on the progression of EMT under high glucose condition in ARPE19 cells could be reversed by miR-204 inhibitor. Also, NEAT1 knockdown inhibited retinal EMT in diabetic mice. Conclusion NEAT1 regulated the development of EMT in DR through miR-204/SOX4 pathway, which could provide reference for clinical prevention and treatment.

Inhibition of Morusin From Mulberry Branches As An Agro-Waste to MDA-MB-453 and HCT116 Cancer Cells By Inducing Cell Apoptosis and Disturbing The Cell Cycle

2021 ◽  
Author(s):  
Zhi-Hao Zhong ◽  
Yu-Qing Zhang
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Epithelial Mesenchymal Transition ◽  
Dependent Manner ◽  
High Concentration ◽  
Mesenchymal Transition ◽  
Silk Industry ◽  
Cancer Migration

Abstract Mulberry tree branches are one of the largest agro-wastes produced in silk industry. How to make full use of this waste has always been one of the most important issues for the silk industry and even the entire biological industry. The paper has first reported that the inhibition of morusin recovered from mulberry branch barks, a prenylated flavonoid, on 20 kinds of tumour cells, of which the IC50 values of the 80% cells reaches about 15 µM. Second, effects on the proliferation, invasion and apoptosis of two cancer cells were investigated in detail. The experimental results showed that the apoptotic ratio of the high concentration was 77.73% in MDA-MB-453 cells. Western blotting displayed that morusin upregulated E-cadherin and downregulated vimentin and N-cadherin in a dose-dependent manner, and thus reversed epithelial-mesenchymal transition. It could upregulate cleaved Caspase-3 and Bax and downregulate Caspase-3 and Bcl-2, which indicate that the cell apoptosis is induced by morusin. These cancer cells, MDA-MB-453, were blocked in G2 phase, and HCT116 were arrested in S phase when treated with morusin, which is possible that the cell cycle is disturbed. Therefore, morusin could inhibit cancer migration and growth and promote cancer cell apoptosis.

scholarly journals MicroRNA-144 Suppresses Prostate Cancer Growth and Metastasis by Targeting EZH2

2021 ◽  
Vol 20 ◽  
pp. 153303382198981
Author(s):  
Xin-bo Sun ◽  
Yong-wei Chen ◽  
Qi-sheng Yao ◽  
Xu-hua Chen ◽  
Min He ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Proliferation And Apoptosis ◽  
High Incidence ◽  
Inhibit Cell Proliferation

Background: Prostate cancer is a common malignant tumor with a high incidence. MicroRNAs (miRNAs) have been shown to be important post-transcriptional regulators during tumorigenesis. This study aimed to explore the effect of miR-144 on PCa proliferation and apoptosis. Material and Methods: The expression of miR-144 and EZH2 were examined in clinical PCa tissues. PCa cell line LNCAP and DU-145 was employed and transfected with miR-144 mimics or inhibitors. The correlation between miR-144 and EZH2 was verified by luciferase reporter assay. Cell viability, apoptosis and migratory capacity were detected by CCK-8, flow cytometry assay and wound healing assay. The protein level of EZH2, E-Cadherin, N-Cadherin and vimentin were analyzed by western blotting. Results: miR-144 was found to be negatively correlated to the expression of EZH2 in PCa tissues. Further studies identified EZH2 as a direct target of miR-144. Moreover, overexpression of miR-144 downregulated expression of EZH2, reduced cell viability and promoted cell apoptosis, while knockdown of miR-144 led to an inverse result. miR-144 also suppressed epithelial-mesenchymal transition level of PCa cells. Conclusion: Our study indicated that miR-144 negatively regulate the expression of EZH2 in clinical specimens and in vitro. miR-144 can inhibit cell proliferation and induce cell apoptosis in PCa cells. Therefore, miR-144 has the potential to be used as a biomarker for predicting the progression of PCa.

scholarly journals GEP100/ARF6 regulates VEGFR2 signaling to facilitate high-glucose-induced epithelial-mesenchymal transition and cell permeability in retinal pigment epithelial cells

2019 ◽  
Vol 316 (6) ◽  
pp. C782-C791 ◽  
Author(s):  
Zhi-Peng You ◽  
Shan-Shan Chen ◽  
Zhong-Yi Yang ◽  
Shu-Rong Li ◽  
Fan Xiong ◽  
...  
Keyword(s):  
Cell Migration ◽  
High Glucose ◽  
Retinal Pigment Epithelial ◽  
Epithelial Mesenchymal Transition ◽  
Retinal Pigment ◽  
Cell Permeability ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Pigment Epithelial ◽  
Vegfr2 Signaling

Cell permeability and epithelial-mesenchymal transition (EMT) were found to be enhanced in diabetic retinopathy, and the aim of this study was to investigate the underlying mechanism. ARPE-19 cell line or primary retinal pigment epithelial (RPE) cells were cultured under high or normal glucose conditions. Specific shRNAs were employed to knock down ADP-ribosylation factor 6 (ARF6), GEP100, or VEGF receptor 2 (VEGFR2) in ARPE-19 or primary RPE cells. Cell migration ability was measured using Transwell assay. Western blotting was used to measure indicated protein levels. RPE cells treated with high glucose showed increased cell migration, paracellular permeability, EMT, and expression of VEGF. Knockdown of VEGFR2 inhibited the high-glucose-induced effects on RPE cells via inactivation of ARF6 and MAPK pathways. Knockdown ARF6 or GEP100 led to inhibition of high-glucose-induced effects via inactivation of VEGFR2 pathway. Knockdown of ARF6, but not GEP100, decreased high-glucose-induced internalization of VEGFR2. High-glucose enhances EMT and cell permeability of RPE cells through activation of VEGFR2 and ARF6/GEP100 pathways, which form a positive feedback loop to maximize the activation of VEGF/VEGFR2 signaling.

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